The objective of this research program is the elucidation of mechanisms responsible for the salt and water retention of congestive heart failure. Congestive failure will be induced in the same conscious dogs by three different methods: 1) inferior vena caval constriction, 2) pulmonary artery stensosis, and 3) aortic stenosis. In addition to the simultaneous measurement of plasma renin activity, plasma aldosterone, plasma catecholamines and plasma antidiuretic hormone, the role of the cardiopulmonary receptors will be assessed in the conscious dog by the cooling of vagal loops. We shall also determine the efficacy of immunologic blockade of renin per se, and of the angiotensin-converting enzyme during the development of failure in animals on normal and low salt intake. The changes in distribution of the converting enzyme in the dog kidney during the production of congestive failure will also be examined. To gain a better understanding of the mechanisms regulating renin storage and release, isolated glomeruli and dissociated granular cells will be grown in the rabbit ear chamber. The development of renin granules will be followed by staining with neutral red dye. The transmembrane potential difference of the granular cells will be determined under varying physiological and pathophysiological states. Finally, by use of electron probe microanalysis we shall define the response of the Na-K-ATPase of the human kidney to diuretic agents, and determine the response of the enzyme system to induction of congestive failure in the dog.